It is generally known that platinum complexes exhibit a broad antitumor effect which is utilized in treatment of a number of tumor diseases. So far, the therapeutic practice makes use only of complexes of bivalent platinum, especially cisplatinum, carboplatinum or oxaliplatinum. However, bivalent platinum complexes are unstable in the gastrointestinal system and/or they are very poorly absorbed. This makes the use of bivalent platinum complexes in an oral, for the patient more advantageous, dosage form impossible. It has been found that some complexes of tetravalent platinum have not this disadvantage and retain their antitumor activity even when administered orally. These complexes of tetravalent platinum were disclosed as novel chemical compounds for oral administration in EP 0 328 274, EP 0 423 707 and PCT/CZ99/00015.
However, complexes of tetravalent platinum are very sparingly soluble in water (about 0.03 g/100 ml), low bulk density (about 0.2 g/ml), low tap density (about 0.4 g/ml), and a high electrostatic charge. The said physical properties represent an important problem for the preparation of a solid oral drug form. Moreover, complexes of tetravalent platinum are chemically unstable in contact with metals or with many currently used excipients. These problems have been solved with partial success in PCT/CZ99/00015 which patent document describes the preparation of solid drug forms of specific tetravalent platinum complexes in the form of inclusion complexes of cyclodextrins with the said tetravalent platinum complexes. According to the mentioned patent document, these inclusion complexes are obtained by reaction of cyclodextrins with complexes of tetravalent platinum in an organic solvent and subsequent lyophilization, and are used for oral application. However, the employed amount of cyclodextrin markedly limits the content of the tetravalent platinum complex present in the oral drug form, which is a disadvantage. The obtained oral drug form thus has a relatively large volume and is difficult to swallow, making a single-dose oral application of higher doses of tetravalent platinum complex impossible.
From what has been said above, it is evident that there is still a need for an oral drug form containing complexes of tetravalent platinum, which drug form would be stable and have a sufficiently high content of the tetravalent platinum complex. To provide such a drug form is the aim of the present invention.